Should children with a history of anaphylaxis to foods undergo challenge testing?

BACKGROUND: Data on the frequency of resolution of anaphylaxis to foods are not available, but such resolution is generally assumed to be rare. OBJECTIVE: To determine whether the frequency of negative challenge tests in children with a history of anaphylaxis to foods is frequent enough to warrant challenge testing to re-evaluate the diagnosis of anaphylaxis, and to document the safety of this procedure. METHODS: All children (n=441) who underwent a double-blind, placebo-controlled food challenge (DBPCFC) between January 2003 and March 2007 were screened for symptoms of anaphylaxis to food by history. Anaphylaxis was defined as symptoms and signs of cardiovascular instability, occurring within 2 h after ingestion of the suspected food. RESULTS: Twenty-one children were enrolled (median age 6.1 years, range 0.8-14.4). The median time interval between the most recent anaphylactic reaction and the DBPCFC was 4.25 years, range 0.3-12.8. Twenty-one DBPCFCs were performed in 21 children. Eighteen of 21 children were sensitized to the food in question. Six DBPCFCs were negative (29%): three for cows milk, one for egg, one for peanut, and one for wheat. In the positive DBPCFCs, no severe reactions occurred, and epinephrine administration was not required. CONCLUSIONS: This is the first study using DBPCFCs in a consecutive series of children with a history of anaphylaxis to foods, and no indications in dietary history that the food allergy had been resolved. Our study shows that in such children having specific IgE levels below established cut-off levels reported in other studies predicting positive challenge outcomes, re-evaluation of clinical reactivity to food by DBPCFC should be considered, even when there are no indications in history that anaphylaxis has resolved. DBPCFCs can be performed safely in these children, although there is a potential risk for severe reactions.

Ready-to-use introduction schedules for first exposure to allergenic foods in children at home.

BACKGROUND: The vast majority of children will undergo their first exposure to common allergenic foods at home. However, the first exposure may lead to clinical reactions. It has been proposed to introduce allergenic foods gradually into the diets of children at risk for food allergy, but no practical dietary advice has been devised. OBJECTIVE: The aim of this study was to devise safe introduction schedules for common allergenic foods for use at home, based on the challenge doses as administered in double-blind, placebo-controlled food challenge (DBPCFCs) in children who were never exposed previously to these foods. METHODS: Seventy-two DBPCFCs were performed in 63 children as a first known exposure. The incrementing challenge doses were converted into equivalent portions of these foods in their usual household form and incorporated in introduction schedules. The feasibility of the introduction scales was tested in parents of the children attending our clinic. RESULTS: Based on the results of the positive challenges (37) in which severe reactions did not occur, detailed introduction schedules and a reference photograph of the required increasing amounts of food were devised for use at home. Feasibility testing showed that, when using these introduction schedules, parents portioned the initial doses significantly lower than without detailed instructions. CONCLUSIONS: The introduction schedules and reference photograph provide information for parents to introduce the required amounts of allergenic foods in initial low doses at home. This is expected to improve the safety of this procedure.

Iron deficiency among children of asylum seekers in the Netherlands.

OBJECTIVES: To investigate, in asylum seekers' children in the Netherlands, biochemical iron status and the prevalence of iron deficiency (ID) and anemia in relation to age, region of origin, length of stay in the Netherlands, body mass index (BMI), and dietary iron intake. PATIENTS AND METHODS: Hemoglobin (Hb) and plasma ferritin concentrations were determined in 122 asylum seekers' children (median age, 7.1 years; range, 2-12 y). ID was defined by plasma ferritin levels <15 microg/L. Anemia was defined by Hb levels <6.8 mmol/L (11 g/dL) for children <6 years of age and Hb levels <7.1 mmol/L (11.5 g/dL) for children between 6 and 12 years of age. Nutritional status of the children was assessed by BMI and dietary intake of iron was estimated by 24-hour recall. RESULTS: Twenty percent of the children had compromised iron status (16% with ID, 4% with ID anemia [IDA]). Another 6% of the children had anemia caused by thalassemia. ID was significantly more prevalent in children <6 years of age and in children of African origin. The iron status was not significantly correlated with the length of stay in the Netherlands (r = 0.6; P = 0.48). Higher BMI z scores were positively correlated with iron status. Adequate or marginal dietary iron intake was not significantly related to the presence of ID (r = 0.02; P = 0.9) or anemia (IDA and thalassemia; r = 0.15; P = 0.9). CONCLUSIONS: Iron deficiency is highly prevalent among the children of asylum seekers in the Netherlands. Our data indicate that systematic biochemical screening for ID is warranted in asylum seekers' children.

Placebo reactions in double-blind, placebo-controlled food challenges in children.

BACKGROUND: A cardinal feature of the double-blind, placebo-controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented. OBJECTIVE: To analyse the occurrence and features of placebo events in DBPCFCs and to assess their contribution to the diagnostic accuracy of the DBPCFC in children. METHODS: The study population consisted of 132 challenges in 105 sensitized children (age range 0.7-16.6 years, median 5.3 years), who underwent DBPCFCs with cow's milk, egg, peanut, hazelnut and soy. Placebo and active food challenges were performed on different days. RESULTS: A total number of 17 (12.9%) positive placebo events occurred, which could be classified as immediate (9/17), late-onset (8/17), objective (11/17) or subjective (6/17). Four of 74 (5.4%) positive active food challenges were revealed to be false positive by administration of a placebo challenge. This is 3% (4/132) of all challenges. When computed by a statistical model, the false positive rate was 0.129 (12.9% of all challenges). CONCLUSION: Placebo events with diverse clinical characteristics occur in DBPCFCs in a significant number of children. The diagnostic significance of the administration of a placebo challenge is first, to identify false positive diagnoses in DBPCFCs by refuting false positive tests in individual patients. Secondly, to allow for blinding of the active food challenge. Thirdly, applying a statistical model demonstrates that some positive challenges may be false positive and that the test may need to be repeated in selected cases.

Dietary intake in asylum seeker children in The Netherlands, strongly related to age and origin.

OBJECTIVE: To monitor the dietary intake of energy, macro- and micronutrients in asylum seeker children. DESIGN AND SETTING: Cross-sectional study in three asylum seeker centres in The Netherlands. SUBJECTS: Hundred and sixteen children 2-12 years old (86% of the study cohort) provided a dietary history. METHOD: The dietary intake was estimated by 24 h recall, and the origin of the children was classified in three geographic regions: African (n=45), Central Asia (n=34) or Eastern Europe (n=37). RESULTS: The total energy intake from fat was in 24% of the children above 40En%. Seventy per cent of the children above 4 year of age had a saturated fat intake above 10En%. The children from Eastern Europe had a higher intake of fat and disaccharides than the children from the other regions. Among the children, an intake less than 80% of the recommended daily allowances of micronutrients was found for calcium (42%), iron (49%), vitamin A (45%) and vitamin D (80%). An inadequate dietary intake of iron and vitamin D was significantly more seen among the youngest children, whereas an inadequate intake of calcium and vitamin A was found more among the elder children. CONCLUSIONS: The dietary intake of a prominent proportion of these children contains too much fat and insufficient amounts of calcium, iron, vitamin A and vitamin D. The low micronutrient intake of the asylum seeker children can be considered as a nutritional risk. Nutritional education and strategies to improve the macro- and micronutrient intake of asylum seeker children is indicated.

Tyrosinemia type I treated by NTBC: how does AFP predict liver cancer?

BACKGROUND: Tyrosinemia type I is associated with an increased risk of liver cancer development. The formation of the pathogenic fumarylacetoacetate is prevented by 2-(2-nitro-4-3 trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC). Still, some patients with NTBC treatment develop liver cancer. A rise of alpha-fetoprotein (AFP) is an indicator of liver cancer. AIM: To study the predictive value of AFP in tyrosinemia type I patients for the discrimination between patients at high and low risk of liver cancer development. METHODS: We examined the course of AFP values of 11 Dutch patients with tyrosinemia type I treated by NTBC, of whom four were diagnosed with liver cancer. RESULTS: The four patients with liver cancer had a course of AFP different from the other patients in either velocity of the decrease of AFP, achieving normal AFP and/or having a rise of AFP concentrations. CONCLUSION: Apart from a rise of AFP, a slow AFP decrease, and never normalizing levels of AFP are important predictors of liver cancer development in further life.

Dietary assessment in children adhering to a food allergen avoidance diet for allergy prevention.

OBJECTIVE: The purpose of this investigation was to verify if avoidance of allergenic foods in children adhering to a food allergen avoidance diet from birth was complete and feasible, and whether dietary assessment can be used as a tool in predicting the outcome of double-blind, placebo-controlled food challenges (DBPCFCs). DESIGN: Children adhering to an allergen avoidance diet from birth underwent DBPCFCs. The investigator-dietician verified whether the elimination was complete, using food frequency questionnaires for common allergenic foods. SETTING: University Medical Centre Groningen, the Netherlands. SUBJECTS: Thiry-eight children aged 1-13 years, who were consecutively referred to the University Medical Centre Groningen for DBPCFC between January 2002 and February 2004. RESULTS: Among the 38 children undergoing DBPCFCs, there were 15 challenges with egg, 15 with peanut, five with hazelnut and three with soy. Fifteen food challenges (39%) were positive. Small quantities of allergenic foods were inadvertently present in the diets of 13 patients (34%), were possibly present in the diets of 14 patients (37%) and could not be identified in the diets of 11 patients (29%). Seven patients (54%) who had inadvertently ingested small quantities of allergenic foods without sequelae had a positive DBPCFC. CONCLUSION: Dietary avoidance was incomplete and not feasible in most cases. Tolerance of small amounts of allergenic foods does not preclude positive challenge reactions. Dietary assessment does not seem a useful tool in predicting the outcome of DBPCFC in children adhering to an elimination diet. SPONSORSHIP: The Stichting Astma Bestrijding (Foundation for the Prevention of Asthma), The Netherlands.

Intestinal transplantation in The Netherlands: first experience and future perspectives.

Intestinal transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients who fail total parenteral nutrition (TPN) therapy. Early referral for evaluation for small bowel transplantation has to be considered in patients with permanent intestinal failure who have occlusion of more than two major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation, and is further improving. Rejection, bacterial, fungal and viral (CMV, EBV) infection, post-transplant lymphoproliferative disease (PTLD) and graft versus host disease (GvHD) are the most common complications after intestinal transplantation. Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects of immunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.

[Small bowel transplantation as a treatment option for intestinal failure in children and adults]. / Dunnedarmtransplantatie als behandeling van darmfalen bij kinderen en volwassenen.

Small bowel transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients where total parenteral nutrition (TPN) therapy for intestinal failure is unsuccessful. Early referral for screening for small bowel transplantation should be considered in patients with permanent intestinal failure who have occlusion of more than 2 major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies, the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation and is further improving. Rejection, bacterial, fungal and viral (Cytomegalovirus, Epstein-Barr-virus) infections, post-transplant lymphoproliferative disease and graft versus host disease are the most common complications after intestinal transplantation. Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects ofimmunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.

[Intestinal rehabilitation for children with short bowel syndrome]. / Darmrevalidatie bij kinderen met een kortedarmsyndroom.

Three children, 2 boys aged 5 and 4 years, and 1 girl aged 2 years, who suffered from intestinal failure as a result of a short bowel syndrome and who were dependent on total parenteral nutrition (TPN), were screened for small bowel transplantation. The girl also had progressive liver failure. Each child had a clear indication for either isolated small bowel or combined small bowel/liver transplantation. All three children were enrolled in an intestinal rehabilitation program because they were referred early. The intestinal rehabilitation consisted of a systematic analysis of the absorptive capacity of the residual intestine, optimizing enteral and parenteral feeding, prevention of catheter sepsis and further deterioration of liver function. The rehabilitation was performed in an in-patient setting. All three children were partially weaned from TPN, while their growth improved. None of the children were consequently listed for small bowel transplantation. When a child is initially referred for small bowel transplantation, intestinal rehabilitation should be considered as part of an intestinal transplantation program.

Renal function in tyrosinaemia type I after liver transplantation: a long-term follow-up.

Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplantation, tyrosinaemia type I was considered to be cured. Some years after the first liver transplantations in these patients, some reports focused on the renal function after transplantation. These reports showed that urinary succinylacetone excretion remained but that tubular function normalized. In this report we discuss the long-term renal follow-up (mean follow-up time 11 years, range 7-14 years) after liver transplantation in 9 patients with tyrosinaemia type I treated by liver transplantation in our centre. An evaluation was made of renal function and succinylacetone excretion in urine. In all patients we found a persistent excretion of succinylacetone in the urine. With respect to the glomerular function, we can conclude that there is no clear change in GFR. At the same time, tubulopathy persisted in some patients. We consider that excretion of metabolites such as succinylacetone will be an important contributing factor to tubular dysfunction after liver transplantation in patients with tyrosinaemia type I. Therefore, notwithstanding the major effect of liver transplantation on tyrosine metabolism, renal tubular dysfunction remains at risk and needs careful monitoring. Progressive tubular dysfunction can cause glomerular damage. The use of low-dose NTBC might be considered after liver transplantation in case of tubulopathy to prevent progression of tubular and glomerular dysfunction.

Juvenile sexual delinquents: contrasting child abusers with peer abusers.

BACKGROUND: There is growing concern regarding juvenile sex offenders, and concomitant interest in a more scientific database which could help direct management and treatment resources. AIMS: To investigate whether juveniles who sexually offend against children (or those at least five years younger than themselves) differ from those who sexually assault their peers or older victims. METHOD: The study is based on data from psychological screenings conducted for the juvenile courts in the Netherlands. RESULTS: As hypothesized, juvenile child molesters scored higher on neuroticism, had experienced more social problems, and had been bullied more often at school than their peers who sexually assaulted same-age or older victims. Child molesters also reported a more negative self-image. When referred for screening, they were younger but had committed more sex offences, more often against males than females. CONCLUSIONS: The results were suggestive of greater need for psychological interventions in the child molester group, although in both groups substantial minorities had had experience of early childhood deprivation or abuse.

[Two sisters with progressive familial intrahepatic cholestasis]. / Twee zusjes met progressieve familiaire intrahepatische cholestase.

A few months after birth two sisters aged 5 and 9 years had developed cholestasis and abnormal liver functions with symptoms including itching and jaundice. The younger sister also developed rickets and clotting disorders. On clinical, biochemical and immunohistopathological grounds the diagnosis of 'progressive familial intrahepatic cholestasis (PFIC) type 2' was made. Medical treatment was not succesfull in reducing symptoms. An ileocolonic bypass in the younger child was not effective. Subsequently, both patients underwent partial external biliary diversion (PEBD). Except for a period of intermittent itching in the younger child, both patients remained free of symptoms 2 years after PEBD. In cases where an early diagnosis is made, PEBD could delay or even prevent the necessity of liver transplantation.

The value of prospective monitoring of Epstein-Barr virus DNA in blood samples of pediatric liver transplant recipients.

UNLABELLED: Post-transplant lymphoproliferative disease (PTLD) is one of the major causes of morbidity and mortality in transplantation patients. A primary Epstein-Barr virus (EBV) infection is a major risk factor for developing PTLD. The aim of this study was to determine circulating EBV DNA after liver transplantation in pediatric patients in relation to primary EBV infection and development of PTLD. EBV serology was performed before transplantation. Every 4 weeks after transplantation a competitive quantitative polymerase chain reaction (PCR) assay for EBV nuclear antigen-1 was performed in 13 patients. Patients were followed for development of a PTLD. Before transplantation four patients were EBV seropositive and nine patients were EBV seronegative. In one of the four patients who were EBV seropositive before transplantation, EBV DNA became detectable after transplantation, with a peak load of 3600 copies/mL. None of these four patients developed a PTLD. Eight of the nine patients who were EBV seronegative before transplantation developed positive EBV DNA samples. EBV DNA was first detected at a mean of 64 days after transplantation (range 38-89). The mean peak EBV DNA load was 79,700 copies/mL (3600-446,000). Two of these patients developed PTLD, but they could not be identified based on prior or concomitant EBV PCR results. CONCLUSIONS: In pediatric liver transplantation EBV DNA load is higher in patients with a primary infection than in patients who were EBV seropositive before transplantation. The EBV PCR cannot be used to identify individual patients who develop PTLD. However, elevated EBV DNA load can be used to detect a group of patients at increased risk for PTLD.

IL-2 loaded dextran microspheres with attractive histocompatibility properties for local IL-2 cancer therapy.

Biodegradable dextran microspheres (MS) were developed as a slow-release system for interleukin-2 (IL-2) to apply them for local IL-2 therapy of cancer. We describe the tissue reactions induced by these MS without or with IL-2 in rats. Dextran MS stain bright red-purple with the periodic acid Schiff (PAS), visualising the exact spot of IL-2 release and its relation to the histological reaction pattern. Subcutaneously injected MS always form a well-circumscribed deposit. In the first 2 days there is a PMN inflammation within the MS-deposit, but the surroundings show only a scanty inflammatory reaction. The PMN reaction is replaced by an abundant macrophage reaction in particular in the MS-deposit. At day 21 a fibrous capsule of about 50 mum surrounds the deposit. The effect of IL-2 administered in its free form is mainly vascular, with vascular dilatation, vascular leakage and oedema. It is remarkable that lymphocytes are present in the injection area already at day 2. When IL-2 releasing MS were used, the various reactions induced by IL-2 and MS were amplified leading to local necrosis. We conclude that neither placebo MS nor IL-2 leads to necrosis after subcutaneous injection in rats. In contrast, when IL-2 was released from MS, then massive necrosis was induced. This might be due to increased phagocytosis or changes in the micro-niche due to the release of humoral factors by the infiltrating cells. This is probably fortuitous for local IL-2 therapy of cancer, as massive necrosis of tumour cells can be expected to lead to an increased antitumour reaction.

[Two children with severe recurrent infections and the X-linked hyper-IgM syndrome]. / Twee kinderen met ernstige, recidiverende infecties en het X-gebonden hyper-IgM-syndroom.

A boy suffered from severe recurrent intestinal infections from the age of 8 months onwards; investigation into an immune disorder ultimately resulted in the diagnosis of 'hyper-IgM syndrome'. He was treated successfully with bone marrow transplantation, using an HLA-matched donor. Another boy had severe recurrent respiratory tract infections from the age of 3 months onwards. At the age of 6.5 years, 'hyper-IgM syndrome' was diagnosed. No suitable donor was available. In addition, he developed sclerosing cholangitis and end-stage liver disease, making a combined bone marrow and liver transplantation too risky. He died at 10.5 years of age. X-linked hyper-IgM syndrome is a rare congenital immunodeficiency disorder, characterised by a defect in both humoral and cellular immune responses. Deficiency in the membrane glycoprotein CD40 ligand (expressed on activated T-cells) compromises T-cell interactions with antigen-presenting cells. In a child with severe recurrent infections, and with dysgammaglobulinaemia with a normal or increased IgM level, the diagnosis of 'X-linked hyper-IgM syndrome' should be considered.

Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds.

The two most common inherited forms of colorectal cancer are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Simultaneous inheritance of both an APC gene mutation and a mismatch repair gene (for example, MLH1) mutation has never been described. In the present case report, we report rapidly progressive adenomatous polyposis in a 10 year old boy with a germline frame shift mutation in the APC gene and a germline splice site mutation in the MLH1 gene. Immunohistochemical investigations showed abnormal expression of beta-catenin in early adenomas with low grade dysplasia, attributed to the APC gene mutation. Subsequent loss of function of the MLH1 gene, as shown by absent immunostaining of its protein in adenomas with high grade dysplasia, may well have caused the rapid progression to high grade dysplasia in many of the adenomas.

Extracorporal albumin dialysis (MARS) improves cholestasis and normalizes low apo A-I levels in a patient with benign recurrent intrahepatic cholestasis (BRIC).

The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile salt levels, therapy-resistant extreme pruritus and peculiar biochemical abnormalities including low apolipoprotein apo A-I. Previously, symptomatic improvement has been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS). We hypothesized that MARS improves cholestasis, induces changes in the bile salt profile and normalizes apo A-I serum levels in BRIC. A 17-year-old-female patient with BRIC experienced an episode of cholestasis lasting for more than 6 months with extreme pruritus and diarrhoea not responding to standard therapy. During a period of five days the patient was treated 3 x 8 h with MARS. The procedures were well tolerated and resulted in reduction of plasma bile salts by 58%. The plasma bile salt profile changed into a more hydrophilic composition after MARS. Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a subjective scale. These effects lasted 4 months until a relapse occurred. Low plasma apo A-I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures were well tolerated. Fatigue was noted as the only transient side-effect. In conclusion, MARS may induce a long-term symptomatic improvement and decrease of cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of MARS in patients with BRIC are needed.

Comparison of outcome after pediatric liver transplantation for metabolic diseases and biliary atresia.

UNLABELLED: Metabolic diseases (MD) are the second largest indication group for orthotopic liver transplantation (OLTx) in children after biliary atresia (BA). A better outcome after transplantation can be expected because of a better pretransplant condition and the absence of previous abdominal surgery. To prove this statement, patient survival, graft survival, and morbidity were compared between a group of 24 for MD and 52 for BA consecutively transplanted children. The actuarial one- and five-year patient survival rates for MD were 96% and 84%, and for BA 84% and 70%, respectively (p logrank test = 0.17). Three MD children (13%) and 15 BA children (29%) died. The actuarial one- and five-year graft survival rates for MD were 75% and 58%, and for BA 75% and 64%, respectively (p logrank test = 0.76). Seven MD children (29%) and 11 BA children (21%) were retransplanted. Postoperative bleeding and gastrointestinal complications occurred less frequent (4% vs. 18% and 4% vs. 14%, respectively), whereas biliary complications, viral infections, and acute rejection occurred more frequently (38% vs. 21%, 29% vs. 15%, and 50% vs. 37%, respectively) in MD children. The difference in the incidence of the various postoperative complications between both groups was not statistically significant. The mean ICU and ventilator stay was 7.5 and four days, respectively, in MD children and 16 and 10 days, respectively, in BA children (p = ns). The mean infection, complication, intervention, and retransplantation rate was equal in both groups. CONCLUSION: Mortality and morbidity after pediatric liver transplantation for MD and BA are not different despite the better starting point for children with MD.

Retransplantation of the liver in children.

BACKGROUND: Because of the poor outcome of hepatic retransplantation, it is still debated whether this procedure should be performed in an era of donor organ scarcity. The aim of this study was to analyze outcome of hepatic retransplantation in children, to identify risk factors influencing this outcome, and to assess morbidity and causes of death. METHODS: A series of 97 children after a single transplantation and 34 children with one retransplantation was analyzed. RESULTS: The 1-, 3-, and 5-year survival of children with a retransplantation was 70, 63, and 52%, respectively, compared with 85, 82, and 78%, respectively, for children after a single transplantation (P=0.009). Survival of children with a retransplantation within 1 month after primary transplantation was worse (P=0.007) and survival of children with a late retransplantation was comparable (P=0.66) with single transplantation. In early retransplantations, the Child-Pugh score was higher, donors were older and weighed more, and more technical variant liver grafts were used compared with single transplantations. Biliary atresia and a high Child-Pugh score were associated with decreased patient survival after retransplantation. Sepsis was the most important complication and cause of death after retransplantation. CONCLUSIONS: Retransplantation is a significant event after pediatric liver transplantation. Outcome after hepatic retransplantation in children is inferior compared with single transplantation. This difference is explained by low survival after early retransplantation and can be explained by the poor clinical condition of the children at time of retransplantation, especially in children with biliary atresia, and by the predominant use of technical variant liver grafts in retransplantations.